Evidence map›Paper›PMID 27428418›Full record

ArticleEBioMedicine2016

A Class of Diacylglycerol Acyltransferase 1 Inhibitors Identified by a Combination of Phenotypic High-throughput Screening, Genomics, and Genetics.

Kirsten Tschapalda, Ya-Qin Zhang, Li Liu, Kseniya Golovnina, Thomas Schlemper, Thomas O Eichmann, Madhu Lal-Nag, Urmila Sreenivasan, John McLenithan, Slava Ziegler and 9 more

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.7field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 15 citations in OpenAlex.

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  4. High-ContentCells · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 9 institutions in 3 countries.

Kirsten TschapaldaSystems Biology of Lipid Metabolism, Heinrich Heine University Düsseldorf, Germany; Institute for Mathematical Modeling of Biological Systems, Heinrich Heine University Düsseldorf, Germany; Department of Chemical Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany; Department of Molecular Developmental Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
Ya-Qin ZhangNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, USA.
Li LiuNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, USA.
Kseniya GolovninaNational Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, USA.
Thomas SchlemperSystems Biology of Lipid Metabolism, Heinrich Heine University Düsseldorf, Germany; Institute for Mathematical Modeling of Biological Systems, Heinrich Heine University Düsseldorf, Germany.
Thomas O EichmannInstitute of Molecular Biosciences, University of Graz, Austria.
Madhu Lal-NagNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, USA.
Urmila SreenivasanDepartment of Medicine, Division of Endocrinology University of Maryland School of Medicine, USA.
John McLenithanDepartment of Medicine, Division of Endocrinology University of Maryland School of Medicine, USA.
Slava ZieglerDepartment of Chemical Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
Carole SztalrydDepartment of Medicine, Division of Endocrinology University of Maryland School of Medicine, USA; Baltimore VA Medical Center, VA Research Service, Geriatric Research, Education and Clinical Center (GRECC) and VA Maryland Health Care System, Department of Medicine, Division of Endocrinology University of Maryland School of Medicine, USA.
Achim LassInstitute of Molecular Biosciences, University of Graz, Austria.
Douglas AuldNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, USA.
Brian OliverNational Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, USA.
Herbert WaldmannDepartment of Chemical Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
Zhuyin LiNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, USA.
Min ShenNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, USA.
Matthew B BoxerNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, USA.
Mathias BellerSystems Biology of Lipid Metabolism, Heinrich Heine University Düsseldorf, Germany; Institute for Mathematical Modeling of Biological Systems, Heinrich Heine University Düsseldorf, Germany. Electronic address: mathias.beller@hhu.de.
National Institutes of Health · USNational Center for Advancing Translational Sciences · USHeinrich Heine University Düsseldorf · DEMax Planck Institute of Molecular Physiology · DEUniversity of Graz · ATUniversity of Maryland, Baltimore · USMax Planck Institute for Biophysical Chemistry · DENational Institute of Diabetes and Digestive and Kidney Diseases · USVA Maryland Health Care System · US

Funding

Drosophila Functional GenomicsZIADK015600 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI OLIVER, BRIAN · 2009 to 2025
$23.9M
Trans-NIH RNAi Facility (TNRF)ZICTR000041 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI CHENG, KEN · 2015 to 2025
$9.4M
Austrian Science Fund FWF P 25193
6 · The paper itself

Abstract

Excess lipid storage is an epidemic problem in human populations. Thus, the identification of small molecules to treat or prevent lipid storage-related metabolic complications is of great interest. Here we screened >320.000 compounds for their ability to prevent a cellular lipid accumulation phenotype. We used fly cells because the multifarious tools available for this organism should facilitate unraveling the mechanism-of-action of active small molecules. Of the several hundred lipid storage inhibitors identified in the primary screen we concentrated on three structurally diverse and potent compound classes active in cells of multiple species (including human) and negligible cytotoxicity. Together with Drosophila in vivo epistasis experiments, RNA-Seq expression profiles suggested that the target of one of the small molecules was diacylglycerol acyltransferase 1 (DGAT1), a key enzyme in the production of triacylglycerols and prominent human drug target. We confirmed this prediction by biochemical and enzymatic activity tests.

Indexed as

GenomicsAnimalsCell DifferentiationCell LineChlorocebus aethiopsCOS CellsDiacylglycerol O-AcyltransferaseDrosophilaEnzyme InhibitorsEpistasis, GeneticFatty AcidsFemaleHumansLipid PeroxidationMaleMiceDiacylglycerol O-AcyltransferaseEnzyme InhibitorsFatty AcidsPyrrolesSmall Molecule Librariesthienopyrrole

Identifiers

PMID27428418
PMCPMC4919474
OpenAlexW2337239566

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.